The objective of this Phase I SBIR proposal is to develop a novel in vivo method for collecting and delivering proteins to the extracellular volume in the central nervous system (CNS). Physiologically significant extracellular proteins include neurotropic factors, cytokines, extracellular enzymes and hormones, of which the pathophysiologic roles are mostly unknown. The immediate application of the proposed method will enable determination of protein function in neurochemical and neuropharmacological research in the brain and spinal cord of whole animals. Potential human applications include drug development and testing, along with clinical diagnostics and drug delivery for alcoholism, Alzheimer's, analgesics, brain tumors, epilepsy, multiple sclerosis and stroke. Specific aims for this novel method are to: 1) develop an optimal LaPP microtube; 2) develop a compatible push-pull microperfusion pump, 3) test the LaPP microtube and push-pull microperfusion pump capability to collect and deliver proteins in vitro. [unreadable] [unreadable] The central element of the technology is a Laser-perforated, Push-Pull Perfused (LAPP) microtube having a protein-exchange zone at the functional end, comprising an array of 10 to 1000 holes of diameters ranging from 1 to 20 microns, and having a bifurcated tubing connection to allow the continuous push-pullregulated perfusion of the outer lumen and inner cannula of the microtube. Semi-automated laser fixturing will be developed to enable fabrication of replicate microtubes having hole arrays of various configurations. In vivo animal experimentation and potential diagnostic applications will be explored in Phase II. [unreadable] [unreadable]